Mo1212 Correlation of GNAS Mutation With Diagnostic Information in Pancreatic Cyst Fluids

Abstract

Background Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are associated with substantially increased risk of malignant transformation when compared to other types of pancreatic lesions such as serous cystadenoma (SCA) and mucinous cystadenoma (MCA). A recent study suggests that detection of a mutation in codon 201 of GNAS in pancreatic cyst fluid DNA may be able to distinguish IPMN from other lesions of the pancreas, including both MCA and SCA [1]. This study found the detection of a GNAS mutation to be 100% specific, and the presence of either a GNAS or KRAS mutation to be 96% sensitive for IPMN. We examined the diagnostic significance of GNAS mutations in a cohort of pancreatic cyst fluid specimens and correlated the results with the associated diagnostic information. Methods 200 residual pancreatic cyst fluid DNA specimens from 198 distinct patients were retrieved from specimen archives and tested. These specimens were chosen so that there was an equal mix of KRAS mutated and wildtype results, and a range of CEA results above and below 192 ng/mL. DNA was amplified with primers targeting the codon 201 region, and sequenced using capillary electrophoresis and Sanger sequencing. The clonality of the mutation was identified as the ratio of mutant to wildtype, with a limit of detection of 10%. IPMN was determined to be present if there was duct dilation or connectivity to the duct system together with observation of mucinous characteristics of the fluid (e.g. gross mucin, mucin stain, elevated CEA, etc.). Results GNAS mutations were found in 50/200 (25%) specimens. A significant association between the presence of KRAS mutation and GNAS mutation was found, with more GNAS mutations present among KRAS-mutated than KRASwildtype cysts (odds ratio=4, p=7.0e-5). There was no significant difference in mean CEA values between according to GNAS mutation status. Two small ( CAT) that has not been previously reported in IPMN; this mutation was present in only that one specimen. In 20/50 (40%) of GNAS mutated-specimens neither duct dilation nor cyst communication with the duct system was observed. Conclusions Based on the present evaluation, GNAS is found to be mutated in a significant number of cases lacking the classic features of IPMNs. Further work is needed to better understand the role of GNAS in discriminating IPMNs from other cystic neoplasms of the pancreas and in evaluating the malignant potential of either; additional surgical outcomes would be valuable for this assessment. 1. Sci. Transl. Med. 3, 92ra66 (2011).